Combination pharmaceutical of temozolomide and mutant idh1 enzyme inhibitor

Abstract

By combining temozolomide with a mutant IDH1 enzyme inhibitor, it was discovered that the dosage of temozolomide could be reduced without decreasing the antitumor effect, enabling us to provide a combination drug with excellent efficacy against cancers with IDH1 mutations.

1 . A pharmaceutical composition, comprising a mutant IDH1 enzyme inhibitor and temozolomide. 
     
     
         2 . (canceled) 
     
     
         3 . The pharmaceutical composition according to  claim 1 , wherein the mutant IDH1 enzyme inhibitor is selected from the group consisting of:
 (i) a compound of Formula (I) or a pharmaceutically acceptable salt thereof;                         (ii) Ivosidenib or a pharmaceutically acceptable salt thereof;   (iii) AG-881 or a pharmaceutically acceptable salt thereof;   (iv) BAY1436032 or a pharmaceutically acceptable salt thereof;   (v) IDH 305 or a pharmaceutically acceptable salt thereof; and   (vi) FT-2102 or a pharmaceutically acceptable salt thereof.   
     
     
         4 . The pharmaceutical composition according to  claim 3 , wherein the mutant IDH1 enzyme inhibitor is the compound of Formula (I) or a pharmaceutically acceptable salt thereof. 
     
     
         5 . The pharmaceutical composition according to  claim 4 , wherein the mutant IDH1 enzyme inhibitor is a tert-butylamine salt of the compound of Formula (I). 
     
     
         6 - 16 . (canceled) 
     
     
         17 . A method of treating cancer, comprising administering to a patient in need thereof an effective amount of a mutant IDH1 enzyme inhibitor in combination with an effective amount of temozolomide. 
     
     
         18 . The method of  claim 17 , wherein the mutant IDH1 enzyme inhibitor and temozolomide are administered simultaneously . 
     
     
         19 . The method  claim 18 , wherein the mutant IDH1 enzyme inhibitor and temozolomide are administered at different times. 
     
     
         20 . The method  claim 17 , wherein the mutant IDH1 enzyme inhibitor is selected from the group consisting of:
 (i) a compound of Formula (I) or a pharmaceutically acceptable salt thereof;                         (ii) Ivosidenib or a pharmaceutically acceptable salt thereof;   (iii) AG-881 or a pharmaceutically acceptable salt thereof;   (iv) BAY1436032 or a pharmaceutically acceptable salt thereof;   (v) IDH 305 or a pharmaceutically acceptable salt thereof; and   (vi) FT-2102 or a pharmaceutically acceptable salt thereof.   
     
     
         21 . The method of  claim 20 , wherein the mutant IDH1 enzyme inhibitor is the compound of Formula (I) or a pharmaceutically acceptable salt thereof. 
     
     
         22 . The method of  claim 21 , wherein the mutant IDH1 enzyme inhibitor is a tert-butylamine salt of the compound of Formula (I). 
     
     
         23 . The method of  claim 17 , wherein the cancer is a cancer having an IDH1 gene mutation. 
     
     
         24 . The method of  claim 17 , wherein the cancer is brain tumor, acute myelogenous leukemia, myelodysplastic syndrome, myeloproliferative tumor, peripheral T-cell lymphoma, chondrosarcoma, osteosarcoma, cholangiocarcinoma, primitive neuroectodermal tumors, B lymphoblastic lymphoma, malignant melanoma, prostate cancer, colorectal cancer, or thyroid cancer. 
     
     
         25 . The method of  claim 24 , wherein the cancer is brain tumor. 
     
     
         26 . The method of  claim 25 , wherein the brain tumor is glioma. 
     
     
         27 . The method of  claim 24 , wherein the cancer is cholangiocarcinoma. 
     
     
         28 . The method of  claim 24 , wherein the cancer is acute myelogenous leukemia. 
     
     
         29 . The method of  claim 24 , wherein the cancer is chondrosarcoma.